Many acute and chronic diseases and disorders are attributable to the injuries from endogenously and exogenously generated reactive oxygen species (“ROS”). ROS injuries occur when the normal detoxifying capability of antioxidant enzymes and vitamins are overwhelmed. Supplements containing recombinant antioxidant enzymes and vitamins treating ROS injuries have revealed some advantages and limitations. Nitric oxide (NO.) and superoxide (O2.) are both physiological gaseous free radicals which alone or in combination are capable of initiating the ROS cascade and injuries. Onging drug development programs target either supplementing or removing NO. Using superoxide dismutase (SOD) as a model, an alternative drug development strategy is to target the removal of O2. and attenuation of follow-on ROS cascade. The latter programs involve mimicking the catalytic activities of SOD in a “metal-center” or a “metal-free” synthetic molecule such as chelated transition metal ion or nitroxide, respectively. The use of polynitroxylated “metal-center” (i.e. polynitroxyl hemoglobin) and “metal-free” (i.e. polynitroxyl albumin) blood proteins as vascular ROS injury protectants and imaging agents is described in patents such as U.S. Pat. Nos. 5,725,839; 5,741,893; 5,767,089; 5,804,561; 5,807,831; 5,817,632; 5,824,781; 5,840,701; 5,591,710; 5,789,376; 5,811,005; 6,048,967. However, it is generally accepted that no one approach can treat all ROS injuries. In fact, continued research efforts have been required to address new challenges not previously envisioned. The present invention shows the existence of a new synthetic analog of a “carboxylate-gated-nitroxide (CGN)” which is a center of activity.
The present invention also shows synthesis of CGN and its “metal-center” and “metal-free” novel compounds in esterified and non-esterified forms and their utility in targeted delivery to therapeutic sites of interest. In addition, conjugation via covalent linking and conjunctive use with existing drugs or targeting molecules increase their therapeutic applications.